Duke University biomedical engineers have grown
three-dimensional human heart muscle that acts just like natural tissue. This
advancement could be important in treating heart attack patients or in serving
as a platform for testing new heart disease medicines.
The "heart patch" grown in the laboratory from
human cells overcomes two major obstacles facing cell-based therapies – the
patch conducts electricity at about the same speed as natural heart cells and
it "squeezes" appropriately. Earlier attempts to create functional
heart patches have largely been unable to overcome those obstacles.
How it works
The source cells used by the Duke researchers were human
embryonic stem cells. These cells are pluripotent, which means that when given
the right chemical and physical signals, they can be coaxed by scientists to
become any kind of cell – in this case heart muscle cells, known as
"The structural and functional properties of these 3-D
tissue patches surpass all previous reports for engineered human heart
muscle," said Nenad Bursac, associate professor of biomedical engineering
at Duke's Pratt School of Engineering. "This is the closest man-made
approximation of native human heart tissue to date."
The results of Bursac's research, which is supported by the
National Heart Lung and Blood Institute, were published on-line in the journal Biomaterials.
Bursac said this approach does not involve genetic
manipulation of cells.
"In past studies, human stem cell-derived
cardiomyocytes were not able to both rapidly conduct electrical activity and
strongly contract as well as normal cardiomyocytes," Bursac said.
"Through optimization of a three-dimensional environment for cell growth,
we were able to 'push' cardiomyocytes to reach unprecedented levels of
electrical and mechanical maturation."
The rate of functional maturation is an important element
for the patch to become practical. In a developing human embryo, it takes about
nine months for a neonatal functioning heart to develop and an additional few
years to reach adult levels of function; however, advancing the functional
properties of these bioengineered patches took a little more than a month,
Bursac said. As technology advances, he said, the time should shorten.
Benefits of the patch
"Currently, it would take us about five to six weeks
starting from pluripotent stem cells to grow a highly functional heart
patch," Bursac said.
"When someone has a heart attack, a portion of the
heart muscle dies," Bursac said. "Our goal would be to implant a
patch of new and functional heart tissue at the site of the injury as rapidly
after heart attack as possible. Using a patient's own cells to generate
pluripotent stem cells would add further advantage in that there would likely
be no immune system reaction, since the cells in the patch would be recognized
by the body as self."
In addition to a possible therapy for patients with heart
disease, Bursac said that engineered heart tissues could also be used to
effectively screen new drugs or therapies.
"Tests or trials of new drugs can be expensive and
time-consuming," Bursac said. "Instead of, or along with testing
drugs on animals, the ability to test on actual, functioning human tissue may
be more predictive of the drugs' effects and help determine which drugs should
go on to further studies."
Some drug tests are conducted on two-dimensional sheets of
heart cells, but according to Bursac, the 3-D culture model provides a superior
environment for functional maturation of cells. This is expected to better
mimic real-world heart muscle responses to different drugs or toxins.
Engineered heart tissues made with cells from patients with a cardiac genetic
disease could be used as the model to study that disease and explore potential
The current experiments were conducted on one human
pluripotent stem cell line. Bursac and his colleagues have reproduced their
findings on two other cell lines and are testing additional lines. They are
also planning to move to larger animal models to learn how the patch would
become functionally integrated with its host and how the patch establishes
connections with the circulatory system.